DESCRIPTION (Applicant's Description): Epidemiologic evidence strongly associates vaccination of cats for rabies and feline leukemia virus with the d e v elopment of soft tissue sarcomas at the vaccine site. Genetic susceptibility, sensitivity to reactive oxygen species (ROS), and chronic low dose environmental exposure to metals may all be significant in the development of this carcinogenesis, as well as in the pathogenesis of human cancer. I propose to carry out studies of vaccine induced tumor genetics and the oxidative status of cats as a potentially informative animal model for solid tumor carcinogenesis. Causative chromosome rearrangement have been i d entified in different human tumors; thus, I will employ classical cytogenetic and such molecular cytogenetic techniques as comparative genomic hybridization (CGH) and Multiplex fluorescence in situ hybridization (M-FISH) t o identify recurrent chromosomal aberrations in feline tumors with significance to carcinogenesis. I am adapting these cytogenetic techniques, designed for human tumors, for use in cats. Sensitivity to ROS in cats with and without vaccine induced tumors will be measured with: 1 ) Blood levels of the antioxidant glutathione in conjunction with indicators of oxidant exposure, oxidized glutathione and malondialdehyde, a product of lipid peroxidation. 2) Oxidative DNA base damage, 8-oxoguanine in particular, quantified by spectrometry of DNA from hydrogen peroxide exposed cat fibroblasts. All of these technologies are in place. Development of pet animal cancer models requires clinical expertise in spontaneous animal tumors combined with laboratory knowledge and skills. I am a veterinary oncologist with abundant clinical experience, currently pursuing a Ph D. I am dedicated to a career in translational cancer research. The Comparative Oncology unit at Colorado State University of which I am a part is dedicated to the development of spontaneous animal tumor models for human cancer and has contributed through the development of experimental therapeutics. I intend to apply the techniques and data acquired from this work to establish a center for animal tumor cytogenetics and genomic to study the role of genetics in the pathogenesis of cancer.